Brain Chemistry and Altitude in Bipolar Disorder

描述(由申请人提供)： 双相情感障碍是一种普遍而严重的精神障碍，以抑郁和躁狂交替发作为特征。在退伍军人事务部，2004年有近8万名退伍军人接受了双相情感障碍的治疗，比1999年增加了40%。双相情感障碍给退伍军人带来了巨大的医疗负担，并与退伍军人管理局系统中所有精神障碍中最高的医疗费用有关。此外，在男性退伍军人中，双相情感障碍是自杀的一个重要风险因素。世界卫生组织将双相情感障碍列为导致全球医疗残疾的第六大原因。尽管进行了几十年的研究，但人们对这种疾病仍然知之甚少，也没有新的治疗方法能超过锂对大多数患者的疗效。迫切需要开展旨在了解双相情感障碍神经生物学的研究，以改进我们的诊断和治疗策略。大脑的PH值与情感功能密切相关，并受到一系列内部和外部因素的影响。其中一个环境因素可能是海拔。极端海拔与吸入氧气的分压降低有关，这种低压低氧会导致严重的认知障碍。然而，海拔适度变化对大脑化学物质的影响还不是很清楚。最近的出版物显示，在美国，海拔高度与自杀率的增加有关，自杀率从大约2000英尺的中等海拔开始，这一影响可能在双相情感障碍中最强。在内源性因素方面，推测双相情感障碍患者的大脑pH值降低可能代表了疾病的一种生物学特征。大脑pH值下降与双相情感障碍患者大脑乳酸和谷氨酸水平改变有关。需要研究来澄清双相情感障碍患者的情绪、脑化学成分和海拔高度之间的关系。为了满足这一需求，我们建议使用磁共振波谱(MRS)神经成像结合临床评估，研究患有双相情感障碍的退伍军人脑pH、谷氨酸、乳酸和海拔之间的关系。该提案采用了一种新颖的横断面研究设计，将在两个海拔高度对双相情感障碍患者进行脑扫描：德克萨斯州盐湖城(4700英尺)和马萨诸塞州贝尔蒙特(44英尺)。共有120名受试者入选，包括40名抑郁双相受试者(每个部位20名)、40名心境良好双相受试者(每个部位20名)和40名健康对照(每个部位20名)。所有受试者都将接受MRS脑部扫描，以测量他们大脑的PH值、谷氨酸和乳酸水平。这项拟议的研究将为双极障碍患者的大脑化学、情绪状态和海拔之间的相互关系提供洞察力。这项研究的结果可能有助于科学家开发新的诊断方法，或为患有双相情感障碍的退伍军人开发新的治疗方法。

DESCRIPTION (provided by applicant): Bipolar disorder is a prevalent and severe psychiatric disorder marked by alternating episodes of depression and mania. In the Department of Veterans Affairs (VA), nearly 80,000 Veterans received care for bipolar disorder in 2004, a 40% increase from 1999. Bipolar disorder imposes a substantial medical burden on Veterans, and is associated with the highest health care costs of any psychiatric disorder in the VA system. Moreover, in male Veterans bipolar disorder is a significant risk factor for suicide. The World Health Organization ranks bipolar disorder as the sixth leading cause of global medical disability. Despite decades of research, the illness remains poorly understood, and no new treatment has surpassed lithium's effectiveness for the majority of patients. There is a critical need for research studies aimed at understanding the neurobiology of bipolar disorder, to improve our diagnostic and treatment strategies. Brain pH is closely linked to affective functioning, and is influenced by a range of internal and external factors. One such environmental factor may be altitude. Extreme altitudes are associated with a decreased partial pressure of inspired oxygen, and this hypobaric hypoxia results in significant cognitive impairment. However, the effect of moderate changes in altitude on brain chemistry is not well understood. Recent publications show that within the U.S., altitude is associated with an increased rate of suicide that begins at the modest altitude of ~2,000 feet, an effect that may be strongest in bipolar disorder. In terms of endogenous factors, it is hypothesized that decreased brain pH in bipolar disorder may represent a biologic trait of the illness. Decreased brain pH has been linked to altered brain lactate and glutamate levels in bipolar disorder. Research is needed to clarify the relationship between mood, brain chemistry and altitude in bipolar disorder. To address this need, we propose to use magnetic resonance spectroscopy (MRS) neuroimaging together with clinical assessments, to study the relationship between brain pH, glutamate, lactate and altitude in Veterans with bipolar disorder. The proposal features a novel cross-sectional study design, in which brain scans will be performed on subjects with bipolar disorder at two altitudes: Salt Lake City, UT (4,700 feet) and Belmont, MA (44 feet). A total of 120 subjects will be enrolled, including 40 depressed bipolar subjects (20 per site), 40 euthymic bipolar subjects (20 per site), and 40 healthy controls (20 per site). All subjects will undergo MRS brain scans to measure their brain pH, glutamate and lactate levels. The proposed study will provide insight into the interrelationship of brain chemistry, mood state and altitude in bipoar disorder. The results of the study may help scientists develop new diagnostic methods, or new treatment approaches for Veterans with bipolar disorder.